Methods for treating aneurysms

ABSTRACT

This invention is directed to methods for treating aneurysms wherein the aneurysmal sac is filled with a non-particulate agent or plurality of such agents and/or with a fluid composition which solidifies in situ. Filling of the aneurysmal sac employs sufficient amount of the non-particulate agent or plurality of such agents and/or the fluid composition to inhibit blood flow into the aneurysm sac. In addition, the methods of this invention also provide for non-endogenous isolation of the parent artery proximal and distal to the aneurysmal sac from systemic blood flow of the treated mammal. The combination of these features provides for treatment of the aneurysmal sac while, at the same time, inhibiting aneurysm formation and/or regrowth in the diseased portions of the arterial wall proximal and distal to the treated aneurysm.

CROSS REFERENCE TO RELATED APPLICATION

[0001] Applicants claim priority to U.S. Provisional Patent ApplicationSerial No. 60/239,777, filed on Oct. 11, 2000, which reference isincorporated by reference herein in its entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] This invention is directed to methods for treating aneurysms in amammalian patient.

[0004] 2. References

[0005] The following publications are cited in this application assuperscript numbers:

[0006] 1. Castaneda-Zuniga, et al., Interventional Radiology, inVascular Embolotherapy, Part 1, 1:9-32, Williams & Wilkins, Publishers(1992)

[0007] 2 Greff, et al., Compositions for Use in Embolizing BloodVessels, U.S. Pat. No. 5,667,767, issued Sep. 16, 1997

[0008] 3 Evans, et al., Cellulose Diacetate Compositions for Use inEmbolizing Blood Vessels,. U.S. Pat. No. 5,580,568, issued Dec. 3, 1996

[0009] 4 Evans, et al., Novel Embolizing Compositions, U.S. Pat. No.5,695,480, issued Dec. 9, 1997

[0010] 5 Jones, et al., Methods for Embolizing Vascular Sites with anEmbolizing Composition Comprising Dimethylsulfoxide, U.S. Pat. No.5,830,178, issued Nov. 3, 1998

[0011] 6 Whalen, et al., Novel Embolizing Compositions Comprising HighPolymer Concentrations, U.S. patent application Ser. No. 09/574,379,filed May 19, 2000

[0012] 7 Evans, et al., Methods for Embolizing Blood Vessels, U.S. Pat.No. 5,702,361, issued Dec. 30, 1997

[0013] 8 Evans, et al., Methods for Embolizing Blood Vessels, U.S. Pat.No. 6,017,977, issued Jan. 25, 2000

[0014] 9 Wallace, et al., Intracranial Stent and Method of Use, U.S.Pat. No. 6,007,573, issued Dec. 28, 1999.

[0015] 10 Racchini, et al., Porous Balloon For Selective Dilation andDrug Delivery, U.S. Pat. No. 5,458,568, issued Oct. 17, 1995

[0016] 11 Whalen, et al., Novel High Viscosity Embolizing Compositions,U.S. patent application Ser. No. 09/574,379, May 19, 2000

[0017] 12 Szikora, et al., Endovascular Treatment of ExperimentalAneurysms with Liquid Polymers: The Protective Potential of Stents,Neurosurgery, 38(2):339-347 (1996)

[0018] 13 Kinugasa, et al., Direct Thrombosis of Aneurysms withCellulose Acetate Polymer, Part II—Preliminary Clinical Experience, J.Neurosurg., 77:501-507 (1992)

[0019] 14 Kinugasa, et al., Cellulose Acetate Polymer Thrombosis for theemergency Treatment of Aneurysms: Angiographic Finding, ClinicalExperience, and Histopathological Study, Neurosurgery, 34:694-701 (1994)

[0020] 15 Mandai, et al., Direct Thrombosis of Aneurysms with CelluloseAcetate Polymer: Part I—Results of Thrombosis in Experimental Aneurysms,J. Neurosurg., 77:497-500 (1992)

[0021] 16 Talia, et al., Bioabsorbable and Biodegradable Stents inUrology, J. Endourology, 11(6):391 (1997)

[0022] 17 Wallace, et al., Intracranial Stent and Method of Use(Delivery System), U.S. application Ser. No. 08/762,110 (pendingapplication).

[0023] 18 Dunn, et al., U.S. Pat. No. 4,938,763 for “BiodegradableIn-Situ Forming Implants and Methods for Producing Same” issued Jul. 3,1990.

[0024] 19 “CANCER, Principles & Practice of Oncology”, 4^(th) Ed.,Volume 1, “Cancer Treatment”, pp. 545-548 (1993).

[0025] All of the above references are herein incorporated by referencein their entirety to the same extent as if each individual reference wasspecifically and individually indicated to be incorporated herein byreference in its entirety

[0026] 3. State of the Art

[0027] Aneurysms arise in mammalian subjects and, in particular, humansubjects as a result of vascular disease wherein the arterial (wall)weakens and, under pressure due to blood flow, the arterial wall“balloons”. Continued growth and/or eventual rupture of the balloonedarterial wall is associated with high morbidity and mortality rates.Intracranial aneurysms are of particular concern because surgicalprocedures to treat these aneurysms before rupture are often notfeasible and further because rupture of these aneurysms can havedevastating results on the patient even if the patient survives rupture.Accordingly, treatment protocols for intracranial aneurysms may beprophylactic in nature, i.e., to inhibit rupture or rerupture of theaneurysm rather than to inhibit bleeding from the ruptured aneurysm.

[0028] Methods well documented in the art to inhibit intracranialaneurysmal rupture include the delivery into the aneurysmal sac ofnon-particulate agents such as metal coils which are designed to inducethrombosis after delivery to the aneurysm thereby inhibiting blood flowinto the aneurysm¹; delivery of a fluid composition into the aneurysmalsac which composition solidifies in the sac to inhibit blood flow intothe aneurysm²⁻⁶; or a delivery of a combination of non-particulateagents and a fluidic composition into the aneursymal sac to inhibitblood flow into the aneurysm.⁷⁻⁸

[0029] In each case, the cranial aneurysm is treated by filling theaneurysmal sac in a manner which inhibits blood flow into the sac. Thisreduced blood flow correlates to reductions in aneurysmal pressure and,hence, a reduction in the likelihood of rupture. However, care must betaken to ensure against migration of non-particulate agents or fluidcomposition beyond the aneurysmal sac (which can occur, for example, byoverfilling of the sac) because this can result in parent artery ordistal embolization which, in turn, has its own high level of morbidityassociated therewith.¹²

[0030] Notwithstanding the benefits that these methods provide ininhibiting aneurysmal rupture, in a significant number of cases, thetreatment protocol is only effective for a short period of time due toreformation of the aneurysmal sac or formation of a new aneurysmal sacat or adjacent the previously treated aneurysm in the treatedpatient.¹³⁻¹⁵

[0031] Upon careful analysis, this invention is based upon the discoverythat subsequent re-treatment arising after initial treatment of theaneurysm by filling the aneurysmal sac with non-particulate agentsand/or fluidic compositions was necessitated because the initialtreatment did not address all of the diseased tissue. Specifically, theaneurysmal sac in the parent artery often reflects only the mostdiseased and hence weakest portion of the arterial wall. However,regions proximal and distal to the aneurysmal sac are often diseased andprone to ballooning. Hence, when the aneurysmal sac is filled via themethods described above, other diseased portions of the arterial walladjacent to the treated aneurysm become more likely to balloon andrupture. It is this latter phenomena that is believed to result inretreatment of the aneurysm.

[0032] While Szikora, et al.¹² discloses the use of a porous stent incombination with a fluid composition in treating an aneurysm, the stentemployed is a porous stent and the amount of polymer employed is lessthan that necessary to completely fill the aneurysmal sac. Accordingly,the techniques disclosed therein do not isolate the parent arteryproximal and distal to the aneurysmal sac from blood flow.

SUMMARY OF THE INVENTION

[0033] This invention is directed to methods for treating aneurysmswherein the aneurysmal sac is filled with a non-particulate agent orplurality of such agents and/or with a fluid composition whichsolidifies in situ. Filling of the aneurysmal sac employs sufficientamount of the non-particulate agent or plurality of such agents and/orthe fluid composition to inhibit blood flow into the aneurysm sac. Inaddition, the methods of this invention also provide for non-endogenousisolation of the parent artery proximal and distal to the aneurysmal sacfrom systemic blood flow of the treated mammal. The combination of thesefeatures provides for treatment of the aneurysmal sac while, at the sametime, inhibiting aneurysm formation and/or regrowth in the diseasedportions of the arterial wall proximal and distal to the treatedaneurysm.

[0034] Preferably, the aneurysm treated is an intracranial (cerebral)aneurysm.

[0035] Accordingly, in one of its method aspects, this invention isdirected to a method for treating an aneurysm in a mammalian patientwhich method comprises:

[0036] (a) identifying the vascular site of an aneurysm in a mammalianpatient wherein said aneurysm comprises an aneursymal sac formed fromthe vascular wall of a parent artery and further wherein said aneurysmalsac participates in the systemic blood flow of said patient;

[0037] (b) inhibiting systemic blood flow into said aneurysmal sac byfilling at least a portion of said sac with a fluid composition and/or anon-particulate agent or plurality of said agents; and

[0038] (c) non-endogenously isolating the parent artery proximal anddistal to said aneurysm from systemic blood flow.

[0039] In the methods described above, the non-particulate agentspreferably comprise metallic coils and, more preferably, platinum coils.

[0040] The fluid composition employed in the methods of this inventionpreferably comprises either a biocompatible polymer or a biocompatibleprepolymer. When a biocompatible polymer is employed, the fluidcomposition preferably comprises a biocompatible polymer, abiocompatible contrast agent, and a biocompatible solvent whichsolubilizes the biocompatible polymer wherein sufficient amounts of thepolymer are employed in the composition such that, upon delivery to theaneurysm, a polymer precipitate forms which fills at least a portion ofthe aneurysmal sac thereby inhibiting blood flow therein. Preferably,the viscosity of the polymer composition is at least about 150 cSt at40° C.

[0041] Such polymer composition can comprise, for example, abiocompatible polymer at a concentration of from about 2 to 50 weightpercent; a biocompatible contrast agent at a concentration of from about10 to about 40 weight percent; and a biocompatible solvent from about 10to 88 weight percent wherein the weight percent of the biocompatiblepolymer, contrast agent and biocompatible solvent is based on the totalweight of the complete composition.

[0042] Preferably, in this particular composition, the concentration ofthe polymer ranges from 6 to 50 weight percent and more preferably 8 to30 weight percent.

[0043] Preferably, the polymer composition has a viscosity of at leastabout 150, preferably at least about 200 and more preferably at least500 cSt at 40° C. More preferably the viscosity ranges from about 200 to40,000 cSt at 40° C., more preferably from about 500 to 40,000 cSt at40° C. In another embodiment, the viscosity ranges from about 500 to5000 cSt at 40° C.

[0044] In another aspect of this invention, the biocompatible polymercan be replaced with a biocompatible prepolymer and, when so used, thepresence of the biocompatible solvent becomes optional.

[0045] In a further preferred embodiment, the biocompatible solvent isdimethylsulfoxide (DMSO), ethanol, ethyl lactate or acetone.

[0046] Isolation of the parent artery proximal and distal to saidaneurysm from systemic blood flow is preferably accomplished byplacement of a stent adjacent the aneurysmal sac which stent extends inboth the proximal and distal directions of the parent artery beyond theaneurysmal sac and isolates blood flow to the arterial walls of theparent artery overlayed by the stent. The stent employed can be eitherformed in situ or placed in the artery by microcatheter techniques.

[0047] Alternatively, the use of novel balloon catheters allow for theuse of fluid compositions to form a coherent precipitate in theaneurysmal sac and which extends from the neck of the sac both distallyand proximally to both fill the aneurysmal sac and to isolate the parentartery from the systemic blood flow both distally and proximally fromthe site of the aneurysm.

[0048] In either case, the methods of this invention entail thenon-endogenous isolation of the parent artery wall to the systemic bloodflow both proximal and distal to the site of the aneurysmal sac. Theparent artery is isolated either immediately adjacent the aneurysmal sacor around the entire inner circumference of the parent artery. Theparent artery is preferably isolated by at least about 2 to 10 mmproximal and distal to said aneurysm from systemic blood flow and morepreferably by no more than about 3 to 5 mm proximal and distal to saidaneurysm.

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The invention will now be described in greater detail withreference to the preferred embodiments illustrated in the accompanyingdrawings, in which like elements bear like reference numerals, andwherein:

[0050]FIG. 1 is a schematic side view of a balloon catheter for use in amethod of treating an aneurysm according to one embodiment of theinvention;

[0051]FIG. 2 is a schematic side view of an alternative embodiment ofthe balloon catheter of FIG. 1 with a double lumen;

[0052]FIG. 3 is a schematic side view of a stent for use in a method oftreating an aneurysm according to the present invention;

[0053]FIG. 4 is a schematic side view of the stent of FIG. 3 positionedin the parent artery near an aneurysm; and

[0054]FIG. 5 is a schematic side view of the stent of FIG. 3 with thefluid composition being delivered to the aneurysm for treatment of theaneurysm.

[0055]FIG. 6 is a schematic side view of the stent of FIG. 3 with thefluid composition filling the aneurysmal sac and the space around thestent's outer surface between the stent and the diseased wall.

DETAILED DESCRIPTION OF THE INVENTION

[0056] This invention is directed to methods for treating aneurysms inmammals. However, prior to discussing this invention in further detail,the following terms will first be defined:

[0057] The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic and substantially non-immunogenic whenused internally in the patient and which are substantially insoluble inthe body fluid of the mammal.

[0058] The biocompatible polymer is preferably non-biodegradable.Suitable non-biodegradable biocompatible polymers include, by way ofexample, cellulose acetates²⁻⁶ (including cellulose diacetate), ethylenevinyl alcohol copolymers, hydrogels (e.g., acrylics), polyacrylonitrile,polyvinylacetate, cellulose acetate butyrate, nitrocellulose, copolymersof urethane/carbonate, copolymers of styrene/maleic acid, and mixturesthereof.

[0059] Biodegradable polymers are disclosed in the art.^(18, 19) Forexample, Dunn, et al.18 discloses the following examples ofbiodegradable polymers: linear-chain polymers such as polylactides,polyglycolides, polycaprolactones, polyanhydrides, polyamides,polyurethanes, polyesteramides, polyorthoesters, polydioxanones,polyacetals, polyketals, polycarbonates, polyorthocarbonates,polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates,polyalkylene oxalates, polyalkylene succinates, poly(malic acid),poly(amino acids), polyvinylpyrrolidone, polyethylene glycol,polyhydroxycellulose, chitin, chitosa, and copolymers, terpolymers andcombinations thereof. Other biodegradable polymers include, for example,fibrin, gelatin, collagen, etc.

[0060] Preferably, the biocompatible polymer employed does not cause anadverse inflammatory reaction when employed in vivo. The particularbiocompatible polymer employed is selected relative to the viscosity ofthe resulting polymer solution, the solubility of the biocompatiblepolymer in the biocompatible solvent, and the like. For example, theselected biocompatible polymer should be soluble in the amounts employedin the selected biocompatible solvent and the resulting compositionshould have a viscosity suitable for in vivo delivery by, e.g.,injection. Such factors are well within the skill of the art.

[0061] Delivery means such as the threaded syringes described, forexample, in U.S. Provisional Patent Application Serial Nos. 60/135,289and 60/135,287, entitled “THREADED SYRINGE” under Attorney Docket No.018413-194 and entitled “SCREW SYRINGE WITH FORCE RELEASE MECHANISM”under Attorney Docket No. 018413-198, both of which were filed on May21, 1999 can be used to assist in delivery of the fluid composition tothe vascular site of the aneurysm, particularly where compositions withhigh viscosities are used. Both of these applications are incorporatedherein by reference in their entirety.

[0062] Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer.

[0063] Cellulose diacetate polymers are either commercially available orcan be prepared by art recognized procedures.

[0064] Ethylene vinyl alcohol copolymers comprise residues of bothethylene and vinyl alcohol monomers. Small amounts (e.g., less than 5mole percent) of additional monomers can be included in the polymerstructure or grafted thereon provided such additional monomers do notalter the properties of the composition. Such additional monomersinclude, by way of example only, maleic anhydride, styrene, propylene,acrylic acid, vinyl acetate and the like.

[0065] The term “contrast agent” refers to a biocompatible radiopaquematerial capable of being monitored during injection into a mammaliansubject by, for example, radiography. The contrast agent can be eitherwater soluble or water insoluble and preferably does not containradioactivity above the native or endogenous amounts naturally occurringin the elements employed (i.e., are “non-radioactive”).

[0066] Examples of water soluble contrast agents include metrizamide,iopamidol, iothalamate sodium, iohexol, iodomide sodium, and meglumine.Examples of water insoluble contrast agents include tantalum, tantalumoxide, and barium sulfate, each of which is commercially available inthe proper form for in vivo use including a preferred particle size ofabout 10 μm or less. Other water insoluble contrast agents include gold,tungsten, and platinum powders.

[0067] Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C.).

[0068] The term “biocompatible solvent” refers to an organic materialliquid at least at body temperature of the mammal in which thebiocompatible polymer is soluble and, in the amounts used, issubstantially non-toxic. Suitable biocompatible solvents include, by wayof example, dimethylsulfoxide, analogues/homologues ofdimethylsulfoxide, ethanol, acetone, ethyl lactate, and the like.Aqueous mixtures with the biocompatible solvent can also be employedprovided that the amount of water employed is sufficiently small thatthe dissolved polymer precipitates upon contact with the blood.Preferably, the biocompatible solvent is dimethylsulfoxide.

[0069] The term “encapsulation” as used relative to the contrast agentbeing encapsulated in the polymer precipitate is not meant to infer anyphysical entrapment of the contrast agent within the precipitate much asa capsule encapsulates a medicament. Rather, this term is used to meanthat an integral coherent precipitate forms which does not separate intoindividual components.

[0070] The term “biocompatible prepolymer” refers to materials whichpolymerize in situ to form a polymer and which, in the amounts employed,are non-toxic and substantially non-immunogenic when used internally inthe patient and which are substantially insoluble in blood. Suitablebiocompatible prepolymers include, by way of example, urethanes,cyanoacrylates, (C1-C6)hydroxyalkyl (C1-C6)alkacrylate (e.g.,hydroxyethyl methacrylate), silicone prepolymers, and the like. Theprepolymer can either be a monomer or a reactive oligomer. Preferably,the biocompatible prepolymer does not cause an adverse inflammatoryreaction when employed in vivo.

[0071] A “stent” is a device which retains integrity of the vascularwall when it is placed in contact with or when it is formed in situadjacent to or in contact with a vascular wall. A stent functions tomaintain patency of a body lumen (such as a vascular wall) and isespecially used as an implant in blood vessels. Stents may be used afterangioplasty to prevent acute re-closure of the blood vessel afterwards.Stents may be utilized after atherectomy, which excises plaque, orcutting balloon angioplasty, which scores the arterial wall prior todilatation, to maintain acute and long-term patency of the vessel.Stents may be utilized in by-pass grafts as well, to maintain vesselpatency. Effectively, a stent overcomes the natural tendency of thevessel walls of some patients to close back down, thereby maintaining amore normal flow of blood through that vessel than would otherwise bepossible if the stent were not in place.

[0072] Suitable stents include open, lattice or porous stents in whichthe structure of the stent is mesh-like in nature having one or moreopenings or pores. The size of at least one of the openings in the stentis preferably large enough to permit a catheter to pass through thestent. Openings of about 0.1 mm to about 10 mm are preferred fortraversal of the catheter through the opening. Openings of about 1.0 mmto about 10 mm are still more preferred for traversal of the catheterthrough the opening.

[0073] Alternatively, stents having one or more grooves (e.g., chevrons)on the surface such that there are cavities created between the stentand the arterial wall can also be employed in the methods of thisinventions.

[0074] A “liquid permeable balloon” is a balloon which comprises atleast a portion of a permeable balloon membrane which membrane allowsthe passage, under positive pressure, of a composition comprising aliquid composition such as a biocompatible polymer or prepolymer, abiocompatible'solvent and a contrast agent. The permeable balloonmembrane is preferably selected to allow the passage of insolubleparticles having a particle size no larger than 10 μm. The positivepressure employed is preferably at least 5 atmospheres, more preferably5 to 75 atmospheres, still more preferably 10 to 50 atmospheres, andfurther more preferably 5 to 30 atmospheres, and still further morepreferably 5 to 20 atmospheres. The permeable material employed in theballoon is not critical provided that it meets the above criteria. Suchmaterials include, by way of example, expanded polytetrafluoroethylene(PTFE, tradename Gortex™), polyethyleneterephthalate (Dacron™, DuPont,Wilmington, Del.), and polyethylene with laser drilled openings. Liquidpermeable balloons are also described by Racchini, et al.¹⁰

[0075] The term “non-particulate agent” refers to biocompatiblemacroscopic solid materials having a discrete physical shape orstructure which, when placed in a blood vessel, result in embolizationof the blood vessel. The non-particulate agents are macroscopic (i.e.,about 1 mm or larger in size) which is contrasted with particulateswhich are microscopic (i.e., less than 1 mm in size). Examples of suchnon-particulate agents include, coils (including metallic coils, coilswith barbs, etc.), silk streamers, plastic brushes, detachable balloons(e.g., silicon or latex balloons), foam (e.g., polyvinyl alcohol foam),nylon mesh and the like. Such non-particulate agents are generallycommercially available. For example, platinum coils are available fromBoston Scientific.

[0076] The specific non-particulate agent employed is not critical andpreferred agents include metallic coils, metallic coils with barbs,metallic coils with fibers (e.g., Dacron® wool fibers) and/or streamers,etc. More preferably, platinum coils are employed.

[0077] “Parent artery” refers to the artery from which the aneurysm isformed.

[0078] “Aneurysms” refer to ballooning of the wall of an artery which,under continued pressure, leads to aneursym growth and/or arterialrupture. Included within this definition are aneurysms which haveruptured but sealed in vivo by, for example, thrombosis. As is apparent,bleeding ceases once the aneurysm has thrombosed.

[0079] “Non-endogenously isolating the parent artery” refers toprocedures for isolating the arterial walls of the parent artery fromsystemic blood flow which procedures do not rely solely upon formationof biological tissue to effect complete isolation of the parent artery.In this regard, growth of endogenous tissue, e.g, over a porous stent,to isolate the parent artery from blood circulation often occurs weeksafter placement of the stent during which time there can be regrowth ofthe aneurysmal sac or formation of a new aneurysm.

[0080] “Proximal ” refers to the surface area of the arterial wall ofthe parent artery radially upstream of the aneurysmal sac, includingarterial wall adjacent to or opposite the aneurysmal sac.

[0081] “Distal ” refers to the surface area of the arterial wall of theparent artery radially downstream of the aneurysm sac, includingarterial wall adjacent to or opposite to the aneurysmal sac.

[0082] “Solidification” refers to the in situ formation of a solid masswhether by the in situ polymerization of a prepolymer in the fluidcomposition or the precipitation of the polymer in the fluidcomposition.

[0083] Compositions

[0084] The polymer or prepolymer compositions employed in the methods ofthis invention are preferably first prepared by conventional methodswhereby each of the components is added and the resulting compositionmixed together until the overall composition is substantiallyhomogeneous.

[0085] For example, polymer compositions can be prepared by addingsufficient amounts of the biocompatible polymer to the biocompatiblesolvent to achieve the effective concentration for the polymercomposition. Preferably, the polymer composition will comprise fromabout 2 to about 50 weight percent of the biocompatible polymercomposition based on the total weight of the polymer composition. Ifnecessary, gentle heating and stirring can be used to effect dissolutionof the biocompatible polymer into the biocompatible solvent, e.g., 12hours at 50° C.

[0086] A sufficient amount of a contrast agent is then added to thecomposition to achieve the effective concentration for the completecomposition. Preferably, the composition will comprise from about 5 toabout 40 weight percent of contrast agent, and still more preferably 10to 40 weight percent of contrast agent.

[0087] The biocompatible solvent preferably comprises from about 40 toabout 90 weight percent of the composition based on the total weight ofthe composition and more preferably about 50 to about 90 weight percent.

[0088] When a water soluble contrast agent is employed, the agent istypically soluble in the solution comprising the non-aqueous solvent andstirring is effected to render the composition homogeneous.

[0089] When a water insoluble contrast agent is employed, the agent isinsoluble in the biocompatible solvent, and stirring is employed toeffect homogeneity,of the resulting suspension. In order to enhanceformation of the suspension, the particle size of the water insolublecontrast agent is preferably maintained at about 10 μm or less and morepreferably at from about 1 to about 5 μm (e.g., an average size of about2 μm).

[0090] In one embodiment, a contrast agent having a particle size ofless than 10 μm is prepared, for example, by fractionation. In such anembodiment, a water insoluble contrast agent such as tantalum, having anaverage particle size of less than about 20 μm, is added to an organicliquid such as ethanol (absolute) preferably in a clean environment.Agitation of the resulting suspension followed by settling forapproximately 40 seconds permits the larger particles to settle faster.Removal of the upper portion of the organic liquid followed byseparation of the liquid from the particles results in a reduction ofthe particle size which is confirmed under an optical microscope. Theprocess is optionally repeated until a desired average particle size isreached.

[0091] The particular order of addition of components to thebiocompatible solvent is not critical and stirring of the resultingsuspension is conducted as necessary to achieve homogeneity of thecomposition. Preferably, mixing/stirring of the composition is conductedunder an anhydrous atmosphere at ambient pressure. The resultingcomposition can be heat sterilized and then stored preferably in sealedbottles or vials until needed.

[0092] Each of the polymers recited herein is commercially available orcan be prepared by methods well known in the art. For example, polymersare typically prepared by conventional techniques such as radical,thermal, UV, γ irradiation, or electron beam induced polymerizationemploying, as necessary, a polymerization catalyst or polymerizationinitiator to provide for the polymer composition. The specific manner ofpolymerization is not critical and the polymerization techniquesemployed do not form a part of this invention.

[0093] In order to maintain solubility in the biocompatible solvent, thepolymers described herein are preferably not cross-linked.

[0094] Further examples of suitable polymer compositions are disclosedby Whalen, et al.¹¹ and Evans, et al.⁴

[0095] Prepolymer compositions can be prepared by adding sufficientamounts of the contrast agent employed in the liquid (e.g., liquidprepolymer) to achieve the effective concentration for the completeprepolymer composition. Preferably, the contrast agent will comprisefrom about 5 to about 40 weight percent of the prepolymer compositionbased on the total weight of the composition.

[0096] When a contrast agent is used which is not soluble in thebiocompatible prepolymer composition, stirring is employed to effecthomogeneity of the resulting suspension. In order to enhance formationof the suspension, the particle size of the insoluble contrast agent ispreferably maintained at about 10 μm or less and more preferably at fromabout 1 to about 5 μm (e.g., an average size of about 2 μm).

[0097] When the prepolymer is liquid (as in the case of cyanoacrylatesor silicone), the use of a biocompatible solvent is not strictlynecessary but may be preferred to provide for an appropriate viscosity,for an appropriate curing time, etc. in the composition. Preferably,when employed, the biocompatible solvent will comprise from about 30 toabout 90 weight percent of the biocompatible prepolymer compositionbased on the total weight of the prepolymer composition, more preferablyfrom about 60 to about 80 weight percent, and still more preferably fromabout 30 to 70. When a biocompatible solvent is employed, theprepolymeric composition typically comprises from about 10 to about 50weight percent of the prepolymer based on the total weight of thecomposition, and more preferably from about 20 to about 60 weightpercent.

[0098] Suitable solvents include iodinated soy bean or poppy seed oilfor cyanoacrylates and water for hydroxyacrylics such as hydroxyethylmethacrylate. In such cases, the oil acts both as a carrier for theprepolymer, a contrast agent and a polymerization time modifier. Othersolvents include hexamethyldisiloxane which is preferably employed inconjunction with silicone.

[0099] In a particularly preferred embodiment, the prepolymer is acyanoacrylate which is preferably employed in a 1:1 ratio with aniodinated oil. When so employed, the cyanoacrylate adhesive is selectedto have a viscosity of from about 5 to about 40 centipoise at 20° C.

[0100] Methods

[0101] This invention is based upon the discovery that subsequentre-treatment of the aneurysm arising after initial treatment of theaneurysm by filling the aneurysmal sac with non-particulate agentsand/or fluidic compositions was necessitated because the initialtreatment did not address all of the diseased tissue. Specifically, theaneurysmal sac in the parent artery often reflects only the mostdiseased and hence weakest portion of the arterial wall. However,regions proximal and distal to the aneurysmal sac are often diseased andprone to ballooning. Hence, when the aneurysmal sac is filled via themethods described above, other diseased portions of the arterial walladjacent to the treated aneurysm become more likely to balloon andrupture. It is this latter phenomena that is believed to result inretreatment of the aneurysm.

[0102] The fluid compositions described above can then be employed inmethods for the catheter assisted treatment of aneurysms in mammalianblood vessels and, in particular, in the treatment of intracranialaneurysms. In such methods, a sufficient amount of the fluid compositionis introduced into the aneurysmal sac via a catheter delivery meansunder fluoroscopy so that upon solidification, the aneurysmal sac issufficiently filled with a solid material to inhibit blood flow therein.Alternatively, the aneurysmal sac can be filled with a sufficient amountof a non-particulate agent or plurality of agents to inhibit blood flowtherein. Still further, a combination of non-particulate agent/agentsand a fluid composition can be employed to fill the aneurysmal sac.

[0103] These methods of delivering non-particulate agents, fluidcompositions or a combination of both to the aneursymal sac to inhibitblood flow into the aneurysm are well known in the art.¹⁻⁸

[0104] The particular amount of materials employed, as viewed by imaging(fluoroscopy), is dictated by the total volume of the aneurysmal sac,the level of filling, the concentration of polymer/prepolymer in thecomposition when a fluid composition is employed, the rate ofprecipitation (solids formation) of the polymer, etc. Such factors arewell within the skill of the art.

[0105] The methods of this invention also entail the non-endogenousisolation of the parent artery wall to the systemic blood flow bothproximal and distal to the site of the aneurysmal sac. The parent arteryis isolated either immediately adjacent the aneurysmal sac or around theentire inner circumference of the parent artery. In this embodiment, theparent artery is preferably isolated by at least about 2 to 10 mmproximal and distal to said aneurysm from systemic blood flow and morepreferably by no more than about 3 to 5 mm proximal and distal to saidaneurysm.

[0106] One method for non-endogenously isolating the parent artery wallfrom the systemic blood flow is the formation of in situ stent using adumbbell balloon as described in detail in Example 3 below. In thatexample, the dumbbell balloon permits filling of the entire aneurysmalsac with a fluid composition which is allowed to overflow the aneurysmalneck to form in situ a stent along the arterial wall byprecipitation/polymerization of the fluid composition. Alternatively,the aneurysmal sac can be sufficiently filled with non-particulate agentvia conventional techniques to inhibit blood flow therein and,subsequently, the dumbbell balloon is placed in the manner of Example 3.Delivery of a fluid composition then results inprecipitation/polymerization of the fluid composition around thenon-particulate agent. In addition, excess fluid composition is employedto permit this composition to overflow the aneurysmal neck to form insitu a stent along the arterial wall by precipitation/polymerization ofthe fluid composition.

[0107] Another method for non-endogenously isolating the parent arterywall from the systemic blood flow is the formation of in situ stentusing a liquid permeable balloon as described in detail in Example 4below. In that example, a fluid composition is delivered to the arterialwalls of the parent artery by the liquid permeable balloon such that theexposed arterial walls are covered by the fluid composition. In situsolidification of the fluid composition results in the formation of astent completely covering the exposed arterial walls of the parentartery.

[0108] Still further, a one-step process for both filling the aneurysmalsac and isolating the parent artery from the systemic blood flow isexemplified in Example 5 below. In this example, a dumbbell stent isemployed which contains an open or porous structure. The open structureis aligned with the aneurysmal sac and then the tip of a microcatheteris fed through the open or porous structure into the aneurysmal sac.Fluid composition is delivered through the catheter tip in a manner suchthat the aneurysmal sac is filled with a sufficient amount of the fluidcomposition to inhibit blood flow into the aneurysm. Further filling isthen conducted to allow overflow of the fluid composition at the neck ofthe aneurysm to encapsulate at least a portion of the open or porousstructure of the stent both proximally and distally to the site of theaneurysm thereby isolating the exposed regions of the parent artery fromblood flow both proximally and distally to the site of the aneurysm.

[0109] In each embodiment, the aneurysmal sac is filled to inhibit bloodflow therethrough while the parent artery is non-endogenously isolatedfrom the systemic blood flow, while still remaining patent. It isimportant to note that, in contrast to the prior art, isolation of theparent artery from the systemic blood flow in the methods of thisinvention does not rely solely upon formation of biological tissue toeffect complete isolation of the parent artery. In this regard, growthof endogenous tissue, e.g, over a porous stent, to isolate the parentartery from blood circulation often occurs weeks after placement of thestent, if at all, during which time there can be regrowth of theaneurysmal sac or formation of a new aneurysm. Thus, for example, use ofa porous or open stent, by itself, will not result in isolation of theparent artery from the blood flow until tissue growth envelops the poresof such stents.

[0110] Alternatively, the porous dumbbell stent described above can bereplaced by a conventional porous stent described, for example, bySzikora, et al.¹² Still further, the stent employed can benon-biodegradable (e.g., made of tantalum filaments) or biodegradable.See, for example, Talia, et al.¹⁶ The use of a biodegradable stentpermits time for formation of tissue over the arterial endothelium whileisolating the arterial wall of the parent artery from blood flow duringformation of this tissue.

[0111] The particular catheters employed in the methods described hereinare not critical provided that polymeric catheter components arecompatible with the embolizing composition (i.e., the cathetercomponents will not readily degrade in the embolizing composition). Inthis regard, it is preferred to use polyethylene in the cathetercomponents because of its inertness in the presence of the embolizingcomposition described herein. Other materials compatible with theembolizing compositions can be readily determined by the skilled artisanand include, for example, other polyolefins, fluoropolymers (e.g.,Teflon™), silicone, etc.

[0112] The following examples are set forth to illustrate the claimedinvention and are not to be construed as a limitation thereof.

EXAMPLES

[0113] Unless otherwise stated, all temperatures are in degrees Celsius.Also, in these examples and elsewhere, the following abbreviations havethe following meanings: cc = cubic centimeter cSt = centiStokes DMSO =dimethylsulfoxide EVOH = ethylene vinyl alcohol copolymer g = gram mg =milligram mL = milliliter ppm = parts per million sec. = seconds μm =micron

Example 1

[0114] The purpose of this example is to demonstrate the preparation oftwo different polymer compositions useful in this invention.

[0115] Composition A

[0116] An EVOH polymer composition was prepared as follows:

[0117] (A) 8 g EVOH (48 mole percent ethylene);

[0118] (B) 30 g tantalum having an average particle size of about 3 μm(narrow size distribution); and

[0119] (C) 100 mL DMSO.

[0120] Each of the components of this composition were combined and theresulting mixture was mixed until homogenous.

[0121] In this composition, the average particle size of the contrastagent was prepared by fractionation wherein tantalum, having an averageparticle size of less than about 20 μm, was added to ethanol (absolute)in a clean environment. Agitation of the resulting suspension wasfollowed by settling for approximately 40 sec. to permit the largerparticles to settle faster. Removal of the upper portion of the ethanolfollowed by separation of the liquid from the particles results in areduction of the particle size which is confirmed under a microscope(Nikon Alphaphot™). The process was repeated, as necessary until anaverage 3 μm particle size was reached.

[0122] Composition B

[0123] approximately 15.1 weight % EVOH (48 mole percent ethylene)

[0124] 18.2 weight % micronized tantalum

[0125] approximately 66.7 weight % DMSO

[0126] Viscosity=approximately 1100 cSt at 40° C.

[0127] In each case, after dissolution of the polymer at 50° C. in DMSOwith stirring, micronized tantalum (average size 3 μm) was then added.The resulting composition was heated for about 5 minutes at 70° C. thenshaken in a vortex mixer for approximately 20 minutes at roomtemperature to obtain a uniform suspension of the insoluble tantalum inthe composition, then heated again for about 5 minutes at 70° C.

Example 2

[0128] The purpose of this example is to demonstrate the preparation ofa prepolymer composition useful in this invention.

[0129] Specifically, a cyanoacrylate prepolymer composition was preparedby adding 800 mg of tantalum powder to 2 g n-butyl cyanoacrylatecontaining 100 ppm SO₂ as a stabilizer to yield a composition comprising28% by weight of tantalum. The ingredients were mixed well, yielding ablack suspension.

Example 3 Formation of In Situ Stent Via Dumbbell Balloon

[0130] The purpose of this example is to demonstrate procedures whichcan be used to inhibit systemic blood flow into an aneurysmal sac andisolation of the parent artery proximal and distal to the aneurysm fromsystemic blood flow by use of a balloon catheter apparatus to form an insitu stent. Generally, the balloon catheter apparatus is formed into adumbbell shape at the vascular site near the aneurysmal sac. The fluidcomposition can then be injected around the narrow portion of thedumbbell to form an in situ stent.

[0131] As shown in FIG. 1, a single lumen catheter body (101) has firstand second ends positioned so that when the first end (103) is locatedin the parent artery on one side of the aneurysmal sac, the second end(105) can be located in the parent artery on the opposite side of theaneurysmal sac. A first inner balloon (107) is bonded over the outsideof the first end of the catheter body. A second inner balloon (109) isbonded over the outside of the second end of the catheter body. Thecatheter includes infusion or inflation holes (111) located in the firstand second end regions of the catheter body covered by the first andsecond balloons to,allow for inflation and deflation of the innerballoons.

[0132] An outer balloon (113) is bonded over the outside of the catheterbody, so that the two inner balloons are entrapped therein. As the twoinner balloons are inflated, the outer balloon is pushed up at the firstand second ends of the catheter body, creating a smooth and continuousdumbbell shaped outer surface of the outer balloon (113). When theapparatus, shown in FIG. 1, is located in the parent artery next to ananeurysm, the end bulges of the outer balloon (113) created by inflationof the inner balloons (107 and 109) are located in the parent artery oneither side of the aneurysmal sac to keep the parent artery patent. Thenarrow portion of the dumbbell shaped outer balloon (113) is located inthe parent artery adjacent the aneurysmal sac and provides a smooth andcontinuous surface for forming and in situ stent. Preferably, the narrowcentral portion of the outer balloon (113) also extends proximal anddistal to the aneurysmal sac and creates a toroidal void into which thefluid composition can be delivered.

[0133] Once the inner balloons have been inflated, a second catheter canbe used to insert a fluid composition into the aneurismal sac and intothe space in the parent artery surrounding the narrow portion of thedumbbell shaped outer balloon, adjacent to, proximal to, and distal tothe aneurysmal sac. Upon delivery, the fluid composition solidifies inthe aneurysmal sac and in the annular space around the narrow portion ofthe outer balloon. After the fluid has solidified, the balloons can bedeflated and the balloon catheter apparatus removed, leaving a in situstent isolating the parent artery proximal and distal to the aneurysmalsac from the systemic blood flow. The in situ stent reinforces the wallof the vasculature at the location of and proximal and distal to theaneurysm and isolates the exposed portions of the parent artery fromblood flow.

[0134] As an alternative embodiment of the above example, the singlelumen balloon catheter can be replaced with a double lumen catheter(201) shown in FIG. 2, where a first lumen (203) provides for theinfusion and inflation of the two inner balloons and a second lumen(205) provides for the infusion and inflation of the outer balloon. Thisdouble lumen catheter embodiment provides for independent control of theinner and outer balloon. Inner balloon infusion holes (207) provide forcontrol of the inner balloons. Outer balloon infusion holes (209)provide for control of the outer balloons.

[0135] According to another alternative embodiment, the dumbbell shapedballoon structure may be replaced with a substantially cylindrical orconstant diameter balloon which has been under inflated. The balloon canact as a trampoline allowing the fluid composition to push the ballooninward filling a space formed between the balloon and the wall of theparent artery with the fluid composition. Upon solidification, theballoon is deflated and removed leaving an in situ stent.

Example 4 Formation of In Situ Stent Via Permeable Balloon

[0136] The purpose of this example is to demonstrate procedures whichcan be used to inhibit systemic blood flow into an aneurysmal sac byfilling the aneurysmal sac with a fluid composition and/ornon-particulate agents, and then isolating the parent artery proximaland distal to the aneurysm by forming an in situ stent near the vascularsite of the aneurysm with the use of a liquid permeable balloon.

[0137] First, the methods described herein employ conventional cathetertechniques to fill the aneurysmal sac with a fluid composition and/ornon-particulate agents, as described above.

[0138] Second, the methods described herein employ conventionalendovascular catheter techniques to direct a liquid permeable ballooncatheter to the vascular site of the aneurysm. The liquid permeableballoon catheter preferably includes an inner impermeable saline filledballoon and an outer permeable balloon positioned coaxially around theinner balloon. Once the liquid permeable balloon catheter is placed atthe selected vascular site, the inner balloon is inflated with saline tolocate and hold the balloon at the vascular site. Positive pressure isthen created within the outer balloon by delivery of the fluidcomposition to the outer balloon. The outer permeable balloon inflatesand intimately contacts the arterial wall of the parent artery. Thepositive pressure is preferably generated in the form of injecting afluid composition comprising a water insoluble biocompatible polymer, abiocompatible solvent and a water insoluble contrast agent into theballoon. Once inflated, the outer balloon is maintained inflated underphysiological conditions for a period of time (e.g., one to ten minutes)to permit a portion of the fluid composition to permeate through holesin the outer permeable balloon and contact the arterial wall of theparent artery. The outer permeable balloon preferably is formed withlaser drilled holes arranged in a pattern selected to achieve thedesired delivery pattern of the fluid composition.

[0139] When the fluid composition is introduced in vivo at the vascularsite through the permeable balloon, the biocompatible solvent diffusesrapidly into the body fluid and a solid, non-migratory precipitate orsolid mass forms which precipitate is the water insoluble polymer andwater insoluble contrast agent encapsulated therein. This precipitatepreferably covers all of the arterial wall of the parent artery which isin contact with the balloon.

[0140] When a prepolymeric composition is introduced in vivo through thefluid permeable balloon, the prepolymer rapidly polymerizes in situ(preferably in less than 15 minutes and more preferably in less than 5minutes) and a solid non-migratory mass forms against the arterial wallof the parent artery which is in contact with the balloon which mass isthe water insoluble polymer and contrast agent encapsulated therein.

[0141] When an adhesive polymer is employed (i.e., cyanoacrylate) careshould be taken to prevent adherence of the cured polymer to theballoon.

[0142] In either case, a solid non-migratory mass forms an in situ stentin the vascular site so that the in situ stent isolates the parentartery of the aneurysm proximal and distal to the aneurysm from thesystemic blood flow. The size and thickness of the in situ stent formedrelate directly to the size and arrangement of holes of the balloonselected as well as the extent and duration of positive pressuremaintained on the inflated balloon. Such factors are well within theskill of the art. Preferably, the in situ formed stent thicknessesformed by the methods of this invention range from about 0.05 mm toabout 1 mm and, more preferably, from about 0.05 mm to about 0.5 mm.

[0143] The in situ stent provides the advantage of preventing theoccurrence of new aneurysms adjacent the treated aneurysm by protectingthe walls of the parent artery proximal and distal to the aneurysm beingtreated. The in situ stent may also provide a surface for endothelialtissue in growth at the aneurysm site and proximal and distal to theaneurysm. The endothelial tissue growth may provide added strengtheningof the parent artery and blood compatibility.

Example 5 Formation of In Situ Stent Via Dumbbell-Shaped MechanicalStent

[0144] The purpose of this example is to demonstrate procedures for theinhibition of systemic blood flow into an aneurysmal sac by filling theaneurysmal sac with a fluid composition and/or non-particulate agents,and isolating the parent artery proximal and distal to the aneurysm byforming an in situ stent near the vascular site of the aneurysm with theuse of a dumbbell shaped mechanical stent.

[0145] According to this embodiment of the invention, a dumbbell-shapedmechanical stent (301), as shown in FIG. 3, is placed in the parentartery adjacent an aneurysmal sac. The mechanical stent has two rigidend segments (303, 305) which can be expanded against the sides of theparent artery in a known manner, e.g., balloon or self expanding, whenthe stent is placed near an aneurysm. The mechanical stent also has aflexible region (307) or open mesh or other open structure located inbetween the two rigid end segments (303, 305). The flexible region (307)of the mechanical stent allows for increased ease of manipulation ortrackability of the stent through the vasculature as the stent isdirected to the site of the aneurysm. This flexible region alsominimizes the amount of blood vessel straightening that can occur as thestent is directed to the site of the aneurysm. The structure of thestent (301) may be formed by a mesh, screen, laser cut tube, lattice,coil, wires, or any other known stent structure.

[0146] The diameter of the flexible central region (307) of themechanical stent is less than the diameter of the rigid end segments(303, 305) of the stent. The stent is preferably delivered and deployedby a dumbbell shaped balloon catheter having a central section with asmaller diameter than end regions. The smaller diameter of the flexiblecentral region (307) of the stent and the corresponding shape of thedumbbell shaped deployment balloon ensures that the flexible region ofthe mechanical stent does not apply any outward distension force to theblood vessel wall of the parent artery after its deployment at thelocation of the aneurysm.

[0147] Upon deployment of the mechanical stent, the more rigid endsegments secure the stent in place and prevent migration by applyingradial distension forces to the walls of the parent artery distal andproximal the aneurysm. As shown in FIG. 4, the smaller diameter centralregion (307) prevents unnecessary pressure from being exerted againstthe weakened section of the parent artery near the aneurysmal sac (401).Even in the case of over-expansion of the stent during deployment, asoften happens in clinical practice, the central region will not applyany radial force on the weakened portion of the parent vessel.

[0148] In FIG. 5, the fluid composition (405) is delivered to theaneurysm sac and the annular space surrounding the central region of themechanical stent by a catheter (403) which may be fed through the openmesh of the central region of the stent. As shown in FIG. 6, the fluidflows into the aneurysmal sac, filling the sac and the space around thestent's outer surface between the stent and the diseased arterial wall.The smaller diameter of the flexible central region of the mechanicalstent allows for the formation of an in situ polymer stent around theparent artery in the region of the smaller diameter, flexible region ofthe mechanical stent. The in situ stent may reinforce the wall of thevasculature at the location of and proximal and distal to the aneurysm.The smaller diameter of the flexible central region also allows thepolymer material to completely isolate a neck of the aneurysm sac andprevent aneurysm regrowth at the neck.

[0149] From the foregoing description, various modifications and changesin the composition and method will occur to those skilled in the art.All such modifications coming within the scope of the appended claimsare intended to be included therein.

What is claimed is:
 1. A method for treating an aneurysm in a mammalianpatient which method comprises: (a) identifying the vascular site of ananeurysm in a mammalian patient wherein said aneurysm comprises ananeursymal sac formed from the vascular wall of a parent artery andfurther wherein said aneurysmal sac participates in the systemic bloodflow of said patient; (b) inhibiting systemic blood flow into saidaneurysmal sac by filling at least a portion of said sac with a fluidcomposition and/or a non-particulate agent or plurality of said agents;and (c) non-endogenously isolating the parent artery proximal and distalto said aneurysm from systemic blood flow.
 2. The method of claim 1,wherein the non-particulate agent or plurality of non-particulate agentscomprise metallic coils.
 3. The method of claim 2, wherein the metalliccoils are platinum coils.
 4. The method of claim 1, wherein the fluidcomposition comprises either a biocompatible polymer or a biocompatibleprepolymer.
 5. The method of claim 4 wherein the fluid compositioncomprises a biocompatible polymer, a biocompatible contrast agent, and abiocompatible solvent which solubilizes the biocompatible polymerwherein sufficient amounts of the polymer are employed in thecomposition such that, upon delivery to the aneurysm, a polymerprecipitate forms which fills at least a portion of the aneurysmal sacthereby inhibiting blood flow therein.
 6. The method of claim 5 whereinthe viscosity of the polymer composition is at least about 150 cSt at40° C.
 7. The method of claim 6 wherein the polymer compositioncomprises a biocompatible polymer at a concentration of from about 2 to50 weight percent; a biocompatible contrast agent at a concentration offrom about 10 to about 40 weight percent; and a biocompatible solventfrom about 10 to 88 weight percent wherein the weight percents of thebiocompatible polymer, contrast agent and biocompatible solvent arebased on the total weight of the complete composition.
 8. The method ofclaim 1, where the fluid composition comprises a biocompatibleprepolymer, a biocompatible contrast agent, and optionally abiocompatible solvent wherein sufficient amounts of the prepolymer areemployed in the composition such that, upon delivery to the aneurysm, apolymer precipitate forms which fills at least a portion of theaneurysmal sac thereby inhibiting blood flow therein.
 9. The method ofclaim 5 wherein the biocompatible solvent is dimethylsulfoxide (DMSO),ethanol, ethyl lactate or acetone.
 10. The method of claim 8 wherein thebiocompatible solvent is dimethylsulfoxide (DMSO), ethanol, ethyllactate or acetone.
 11. The method of claim 1 wherein isolation of theparent artery proximal and distal to said aneurysm from systemic bloodflow is accomplished by placement of a stent adjacent the aneurysmal sacwhich stent extends in both the proximal and distal directions of theparent artery beyond the aneurysmal sac and isolates blood flow to thearterial walls of the parent artery overlayed by the stent.